Department of Pathology and Laboratory Medicine, Warren Alpert Medical School, Brown University, Providence, RI, United States.
Department of Internal Medicine, University of South Florida, Tampa, FL, United States.
Front Immunol. 2024 May 28;15:1350560. doi: 10.3389/fimmu.2024.1350560. eCollection 2024.
Despite decades of effort, malaria remains a leading killer of children. The absence of a highly effective vaccine and the emergence of parasites resistant to both diagnosis as well as treatment hamper effective public health interventions.
To discover new vaccine candidates, we used our whole proteome differential screening method and identified PfGBP130 as a parasite protein uniquely recognized by antibodies from children who had developed resistance to infection but not from those who remained susceptible. We formulated PfGBP130 as lipid encapsulated mRNA, DNA plasmid, and recombinant protein-based immunogens and evaluated the efficacy of murine polyclonal anti-PfGBP130 antisera to inhibit parasite growth in vitro. Immunization of mice with PfGBP130-A (aa 111-374), the region identified in our differential screen, formulated as a DNA plasmid or lipid encapsulated mRNA, but not as a recombinant protein, induced antibodies that inhibited RBC invasion . mRNA encoding the full ectodomain of PfGBP130 (aa 89-824) also generated parasite growth-inhibitory antibodies.
We are currently advancing PfGBP130-A formulated as a lipid-encapsulated mRNA for efficacy evaluation in non-human primates.
尽管经过了几十年的努力，疟疾仍然是儿童的主要杀手。缺乏高度有效的疫苗以及诊断和治疗都耐药的寄生虫，阻碍了有效的公共卫生干预措施的实施。
为了发现新的疫苗候选物，我们使用了我们的全蛋白质组差异筛选方法，鉴定出 PfGBP130 是一种寄生虫蛋白，仅被已经对感染产生耐药性的儿童的抗体识别，而未被仍然易感的儿童的抗体识别。我们将 PfGBP130 制成脂质包裹的 mRNA、DNA 质粒和重组蛋白免疫原，并评估了小鼠多克隆抗 PfGBP130 抗血清抑制寄生虫在体外生长的功效。用 PfGBP130-A（aa111-374）免疫小鼠，该区域是我们的差异筛选中确定的，制成 DNA 质粒或脂质包裹的 mRNA，但不是重组蛋白，可诱导抗体抑制 RBC 入侵。PfGBP130 的全长外显子（aa89-824）编码的 mRNA 也产生了抑制寄生虫生长的抗体。
我们目前正在推进 PfGBP130-A 作为脂质包裹的 mRNA 进行非人类灵长类动物的功效评估。
